Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice

Although L-Asparaginase (L-ASP) is an effective chemotherapeutic agent, it has side effects such as fever, skin rashes, chills, anaphylaxis, and severe allergic reactions. Moreover, the short half-life of L-ASP reduces its antitumor activity. To reduce its side effects and broaden its pharmaceutical...

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Main Authors: Thi Thao Do, Thi Phuong Do, Thi Nga Nguyen, Thi Cuc Nguyen, Thi Thu Phuong Vu, Thi Giang An Nguyen
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Advances in Materials Science and Engineering
Online Access:http://dx.doi.org/10.1155/2019/3534807
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author Thi Thao Do
Thi Phuong Do
Thi Nga Nguyen
Thi Cuc Nguyen
Thi Thu Phuong Vu
Thi Giang An Nguyen
author_facet Thi Thao Do
Thi Phuong Do
Thi Nga Nguyen
Thi Cuc Nguyen
Thi Thu Phuong Vu
Thi Giang An Nguyen
author_sort Thi Thao Do
collection DOAJ
description Although L-Asparaginase (L-ASP) is an effective chemotherapeutic agent, it has side effects such as fever, skin rashes, chills, anaphylaxis, and severe allergic reactions. Moreover, the short half-life of L-ASP reduces its antitumor activity. To reduce its side effects and broaden its pharmaceutical applications, L-ASP obtained from Pectobacterium carotovorum was subjected to liposomal conjugation. The enzyme was then loaded into liposomes using the hydrated thin-film method. The in vitro cytotoxic activity of liposomal L-ASP was evaluated with the MTT assay using cancerous cell lines, and its antitumor effects were examined in Lewis lung carcinoma (LLC) tumorized mice. The average size of the liposomes containing purified L-asparagine was 93.03 ± 0.49 nm. They had a zeta potential of –15.45 ± 6.72 mV, polydispersity index of 0.22 ± 0.02, and encapsulation efficiency of 53.99 ± 5.44%. The in vitro cytotoxic activity of liposomal L-ASP was less effective against LLC, MCF-7 (human breast carcinoma), HepG2 (human hepatocellular carcinoma), SK-LU-1 (human lung carcinoma), and NTERA-2 (pluripotent human embryonic carcinoma) cells than that of free L-ASP. However, the antitumor activity of liposomal L-ASP was significantly greater than that of untrapped L-ASP at the same doses (6 UI/mouse) in terms of tumor size (6309.11 ± 414.06 mm3) and life span (35.00 ± 1.12 days). This is the first time the antitumor activities of PEGylated nanoliposomal L-ASP have been assessed in LLC carcinoma tumor-induced BALB/c mice and showed significantly improved pharmacological properties compared to those of free L-ASP (P<0.05). Thus, nanoliposomal L-ASP should be considered for its widening applications against carcinoma tumors.
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spelling doaj-art-a4f7740ff00c4a249a0e377911fe17bb2025-02-03T01:31:42ZengWileyAdvances in Materials Science and Engineering1687-84341687-84422019-01-01201910.1155/2019/35348073534807Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c MiceThi Thao Do0Thi Phuong Do1Thi Nga Nguyen2Thi Cuc Nguyen3Thi Thu Phuong Vu4Thi Giang An Nguyen5Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Nghia Do, Cau Giay, Ha Noi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Nghia Do, Cau Giay, Ha Noi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Nghia Do, Cau Giay, Ha Noi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Nghia Do, Cau Giay, Ha Noi, VietnamInstitute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Nghia Do, Cau Giay, Ha Noi, VietnamSchool of Natural Sciences Education, Vinh University, 182 Le Duan Str, Vinh, Nghe An Province, VietnamAlthough L-Asparaginase (L-ASP) is an effective chemotherapeutic agent, it has side effects such as fever, skin rashes, chills, anaphylaxis, and severe allergic reactions. Moreover, the short half-life of L-ASP reduces its antitumor activity. To reduce its side effects and broaden its pharmaceutical applications, L-ASP obtained from Pectobacterium carotovorum was subjected to liposomal conjugation. The enzyme was then loaded into liposomes using the hydrated thin-film method. The in vitro cytotoxic activity of liposomal L-ASP was evaluated with the MTT assay using cancerous cell lines, and its antitumor effects were examined in Lewis lung carcinoma (LLC) tumorized mice. The average size of the liposomes containing purified L-asparagine was 93.03 ± 0.49 nm. They had a zeta potential of –15.45 ± 6.72 mV, polydispersity index of 0.22 ± 0.02, and encapsulation efficiency of 53.99 ± 5.44%. The in vitro cytotoxic activity of liposomal L-ASP was less effective against LLC, MCF-7 (human breast carcinoma), HepG2 (human hepatocellular carcinoma), SK-LU-1 (human lung carcinoma), and NTERA-2 (pluripotent human embryonic carcinoma) cells than that of free L-ASP. However, the antitumor activity of liposomal L-ASP was significantly greater than that of untrapped L-ASP at the same doses (6 UI/mouse) in terms of tumor size (6309.11 ± 414.06 mm3) and life span (35.00 ± 1.12 days). This is the first time the antitumor activities of PEGylated nanoliposomal L-ASP have been assessed in LLC carcinoma tumor-induced BALB/c mice and showed significantly improved pharmacological properties compared to those of free L-ASP (P<0.05). Thus, nanoliposomal L-ASP should be considered for its widening applications against carcinoma tumors.http://dx.doi.org/10.1155/2019/3534807
spellingShingle Thi Thao Do
Thi Phuong Do
Thi Nga Nguyen
Thi Cuc Nguyen
Thi Thu Phuong Vu
Thi Giang An Nguyen
Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice
Advances in Materials Science and Engineering
title Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice
title_full Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice
title_fullStr Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice
title_full_unstemmed Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice
title_short Nanoliposomal L-Asparaginase and Its Antitumor Activities in Lewis Lung Carcinoma Tumor-Induced BALB/c Mice
title_sort nanoliposomal l asparaginase and its antitumor activities in lewis lung carcinoma tumor induced balb c mice
url http://dx.doi.org/10.1155/2019/3534807
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